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白细胞介素-18基因启动子区域多态性与中国汉族女性散发性乳腺癌易感性的关联分析

Association analysis of interleukin-18 gene promoter region polymorphisms and susceptibility to sporadic breast cancer in Chinese Han women.

作者信息

Qiao Xuefeng, Xu Danfei, Sun Dandan, Sun Sijin, Huang Zhiping, Cui Wei

机构信息

Department of Clinical Laboratory, Beijing Meitan General Hospital, Beijing, China.

Clinical Laboratory, Peking Union Medical College, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

J Clin Lab Anal. 2018 Nov;32(9):e22591. doi: 10.1002/jcla.22591. Epub 2018 Jun 21.

Abstract

BACKGROUND

Interleukin-18-137G/C, -607G/T polymorphisms play multiple roles in various cancers. However, studies focused on its involvement in breast cancer remain controversial, and no study has taken the interaction between interleukin-18 (IL-18) gene polymorphism and body mass index (BMI), menopause into consideration. The study investigated the association between IL-18-137, -607 polymorphisms and risk of breast cancer and a possible interaction between the 2 single nucleotide polymorphisms (SNPs) and BMI, menopause in Chinese Han woman.

METHODS

A total of 488 participants, including 178 patients with breast cancer, 150 patients with benign breast disease and 160 healthy controls were recruited for this study. Polymerase chain reaction (PCR)-direct sequencing technology was used to identify the genotypes.

RESULTS

137 G/C genotype can decrease the risk of breast cancer (OR = 0.54, 95% CI: 0.31-0.93; P = .025). In benign group, subjects with G/C genotype of IL-18-137G/C polymorphism had a 1.89-fold increased risk of developing breast cancer (95% CI = 1.05-3.41; P = .032). Among postmenopausal subjects, people with G/T genotype of IL-18-607 polymorphism had a 7.97-fold increased risk of lymph node metastasis compared with those with T/T homozygotes (95% CI = 1.95-32.65; P = .0045). Among Overweight and obese patients with breast cancer (BMI ≥ 24), people with G/T genotype of IL-18-607 polymorphism had a 5.45-fold increased risk of lymph node metastasis compared with those with T/T homozygotes (95% CI = 1.74-17.06; P = .034).

CONCLUSIONS

IL-18-137 G/C genotype may be a protective factor for healthy group, but a risk factor for benign group. IL-18-607 G/T genotype have an interaction with menopausal and BMI. The synergetic effect can further increase the risk of lymph node metastasis for breast cancer patients.

摘要

背景

白细胞介素-18(IL-18)-137G/C、-607G/T基因多态性在多种癌症中发挥多种作用。然而,关于其在乳腺癌中的作用的研究仍存在争议,且尚无研究考虑IL-18基因多态性与体重指数(BMI)、绝经之间的相互作用。本研究调查了中国汉族女性中IL-18 -137、-607基因多态性与乳腺癌风险之间的关联,以及这两种单核苷酸多态性(SNP)与BMI、绝经之间可能存在的相互作用。

方法

本研究共招募了488名参与者,包括178例乳腺癌患者、150例乳腺良性疾病患者和160名健康对照。采用聚合酶链反应(PCR)-直接测序技术鉴定基因型。

结果

137G/C基因型可降低乳腺癌风险(OR = 0.54,95%CI:0.31 - 0.93;P = 0.025)。在良性疾病组中,IL-18 -137G/C基因多态性为G/C基因型的受试者患乳腺癌的风险增加1.89倍(95%CI = 1.05 - 3.41;P = 0.032)。在绝经后受试者中,IL-18 -607基因多态性为G/T基因型的人群发生淋巴结转移的风险是T/T纯合子人群的7.97倍(95%CI = 1.95 - 32.65;P = 0.0045)。在超重和肥胖的乳腺癌患者(BMI≥24)中,IL-18 -607基因多态性为G/T基因型的人群发生淋巴结转移的风险是T/T纯合子人群的5.45倍(95%CI = 1.74 - 17.06;P = 0.034)。

结论

IL-18 -137G/C基因型可能是健康人群的保护因素,但却是良性疾病人群的危险因素。IL-18 -607G/T基因型与绝经和BMI存在相互作用。这种协同效应可进一步增加乳腺癌患者发生淋巴结转移的风险。

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